The stereochemical course of most kinetically controlled reactions is determined by a combination of steric and/or stereoelectronic factors. This proposal requests support, as part of an ongoing program, to determine the importance of these factors in determining the stereochemical outcome of the three superficially simple reactions outlined in Diagram I; mainly, nucleophilic additions to various substituted tetrahydropyridinium salts (1), electrophilic additions to substituted 2-piperideines (2), and the annulation of these endocyclic enamines with various enones to produce substituted hydroindolones (4). The results of this study are cumulative and should provide a powerful heuristic for the stereorationale design of alkaloid syntheses. A high premium is also placed on efficiency of bond construction. The research will be conducted in three overlapping phases. In phase I we hope to conclude studies already underway on efficient hopefully stereospecific total syntheses of the indole alkaloids RESERPINE and 3-EPI-Alpha-YOHINBINE, the lycopodium alkaloid FAWCETTIINE, the cardiotoxic alkaloids PUMILIOTOXIN C and PERHYDROGEPHYROTOXIN and the novel perhydro[9b]azaphenalene base PORANTHERICINE. As these projects are completed, work on the total synthesis of the indole alkaloids VINOXINE, CONDYLOCARPIN AKUAMMICINE, the WIELAND-GUMLICH ALDEHYDE and STRYCHNINE, and PSEUDOAKUAMMIGINE. These studies will lead into phase III and may include the following targets: AKUAMMICINE, AKUAMMILINE, APPARICINE, ASPIDODASYCARPINE, CATHOFOLINE, STEMMADENINE, STRICTAMINE, QUATERNOLINE and VALLESAMINE.